Cadherins provide strong calcium dependent cell-cell adhesion. They are differentially localized in the CNS and have been proposed to play major roles in both neurite outgrowth and synapse formation. Here we propose to examine the role classic cadherins have in forming functionally distinct pathways and synapses in the limbic system. The first aim will be to identify and localize the classic cadherins expressed in the limbic system during the final stages of pathfinding and synaptogenesis. To do this, RT-PCR will be used to amplify cadherins from the hippocampus. Using in-situ hybridization, the regional laminar and cellular localization of different cadherins will be determined over time. Using antibodies to particular cadherins and synaptic proteins, double-labeling techniques and tract tracing will identify the cells, circuits and synapses in which a defined group of classic cadherins play in the development of connectivity in the CA3 region of the hippocampus. To achieve this end, function blocking antibodies, peptides and dominant-negative constructs will be used to determine what effect blocking N-cadherin has on the development of the mossy fiber synaptic terminals. Together these aims will address the precise role that cadherins play in the formation and specification of neuronal connections.